Detector with reduced fluorescence range noise

ABSTRACT

There is set forth herein a device comprising structure defining a detector surface configured for supporting biological or chemical substances, and a sensor array comprising light sensors and circuitry to transmit data signals using photons detected by the light sensors. The device can include one or more features for reducing fluorescence range noise in a detection band of the sensor array.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.16/948,524, filed Sep. 22, 2020, entitled “Detector With ReducedFluorescence Range Noise,” which is a continuation of U.S. applicationSer. No. 16/778,935, filed Jan. 31, 2020, entitled “Detector WithReduced Fluorescence Range Noise,” which is a continuation of U.S.application Ser. No. 16/206,564, filed Nov. 30, 2018, now U.S. Pat. No.10,551,317, issued Feb. 4, 2020, entitled “Detector With ReducedFluorescence Range Noise,” which claims priority to U.S. PatentApplication No. 62/611,464, filed Dec. 28, 2017, entitled “Detector WithReduced Fluorescence Range Noise” and U.S. Patent Application No.62/644,804, filed Mar. 19, 2018, entitled “Detector With ReducedFluorescence Range Noise.” The entire contents of each of theaforementioned applications are incorporated herein by reference.

BACKGROUND

Various protocols in biological or chemical research involve performingcontrolled reactions. The designated reactions can then be observed ordetected and subsequent analysis can help identify or reveal propertiesof chemicals involved in the reaction.

In some multiplex assays, an unknown analyte having an identifiablelabel (e.g. fluorescent label) can be exposed to thousands of knownprobes under controlled conditions. Each known probe can be depositedinto a corresponding well of a microplate. Observing any chemicalreactions that occur between the known probes and the unknown analytewithin the wells can help identify or reveal properties of the analyte.Other examples of such protocols include known DNA sequencing processes,such as sequencing-by-synthesis (SBS) or cyclic-array sequencing.

In some fluorescent-detection protocols, an optical system is used todirect excitation light onto fluorophores, e.g. fluorescently-labeledanalytes and to also detect the fluorescent emissions signal light thatcan emit from the analytes having attached fluorophores. However, suchoptical systems can be relatively expensive and require a largerbenchtop footprint. For example, the optical system can include anarrangement of lenses, filters, and light sources.

In other proposed detection systems, the controlled reactions in a flowcell define by a solid-state light sensor array (e.g. a complementarymetal oxide semiconductor (CMOS) detector or a charge coupled device(CCD) detector). These systems do not involve a large optical assemblyto detect the fluorescent emissions.

BRIEF DESCRIPTION

There is set forth herein a device comprising: structure defining adetector surface configured for supporting biological or chemicalsubstances, and a sensor array comprising light sensors and circuitry totransmit data signals using photons detected by the light sensors. Thedevice can include one or more feature for reducing fluorescence rangenoise in a detection band of the sensor array.

There is set forth herein a device comprising: a structure defining adetector surface configured for supporting biological or chemicalsamples; and a sensor array comprising light sensors and circuitry totransmit signals using photons detected by the light sensors; a guidearray comprising light guides; wherein light guides of the guide arrayreceive excitation light and emissions signal light from the detectorsurface, wherein the light guides extend toward respective light sensorsof the sensor array and comprise filter material that blocks theexcitation light and permits the emissions signal light to propagatetoward the respective light sensors, and wherein the filter materialcomprises a metal complex dye.

There is set forth herein a method comprising: fabricating circuitry totransmit data signals using photons detected by a light sensor array;depositing filter material within guide cavities of a guide cavity arraythat are aligned with and disposed above respective light sensors of thelight sensor array, wherein the filter material comprises dye suspendedin a polymer matrix, the dye comprising a photon emission quencher; andfabricating a structure defining a detector surface for supportingbiological or chemical samples, wherein the fabricating the structuredefining the detector surface includes fabricating the structuredefining the detector surface above cavities of the guide cavity arrayand light sensors of the light sensor array.

There is set forth herein a device comprising: a structure defining adetector surface for supporting biological or chemical samples; a sensorarray comprising light sensors, and circuitry to transmit data signalsbased on photons detected by the light sensors; and a guide arraycomprising light guides; wherein light guides of the guide array receiveexcitation light and emissions signal light from the detector surface,wherein the light guides extend toward respective light sensors of thesensor array and comprise filter material that blocks the excitationlight and permits the emissions signal light to propagate toward therespective light sensors, wherein the detector surface includes areaction recess, the reaction recess comprising an index of refractionand a dimension sufficient to cancel background light energy incident onthe detector surface in a detection band of the sensor array.

DRAWINGS

These and other features, aspects, and advantages of the present subjectmatter will become better understood when the following detaileddescription is read with reference to the accompanying drawings in whichlike characters represent like parts throughout the drawings, wherein:

FIG. 1 is a schematic cutaway side view of a system for use inbiological or chemical analysis having a detector that includes adetector surface for supporting a biological or chemical sampleaccording to one example;

FIG. 2 spectral profile coordination diagram illustrating coordinationbetween excitation wavelengths, absorption wavelengths, fluorescenceemissions signal wavelengths, and detection band wavelengths accordingto one example;

FIG. 3 is spectral profile diagram illustrating autofluorescencecharacteristics of filter materials according to one example;

FIG. 4 is an energy state transition diagram illustrating energy statetransitions of a radiant dye according to one example;

FIG. 5 is an energy state transition diagram illustrating energy statetransitions of a dye having a photon emission quencher according to oneexample;

FIG. 6 is an energy state transition diagram illustrating energy statetransitions of a metal complex dye having a photon emission quencheraccording to one example;

FIG. 7 depicts optical density (OD) by film thickness diagramillustrating dependence of OD on film thickness for a filter materialhaving a metal complex dye according to one example;

FIG. 8 is a cutaway side view of a detector having a detector surfaceconfigured to cancel incident light energy in selective wavelength bandsaccording to one example;

FIG. 9 is a cutaway side view of a detector having a sensor array, alight guide array and a reaction array according to one example; and

FIG. 10 is a cutaway side view of a detector having a light sensor, alight guide, and reaction recess defined by a detector surface accordingto one example.

DETAILED DESCRIPTION

In FIG. 1 there is shown a system 100 for use in analysis, such asbiological or chemical analysis. System 100 can include light energyexciter 10 and a detector assembly 20. Detector assembly 20 can includedetector 200 and a flow cell 282. Detector 200 can include a pluralityof light sensors 202 and detector surface 206 for supporting samples 502such as biological or chemical samples subject to test. Detector 200 canalso include a plurality of light guides that guide light from detectorsurface 206 to light sensors 202. Detector surface 206, sidewalls 284,and flow cover 288 can define and delimit flow cell 282. Detectorsurface 206 can have an associated detector surface plane 130.

In a further aspect, detector surface 206 can be recessed to includereaction recesses 210 (nanowells). According to one example, each lightsensor 202 can be aligned to one light guide 214 and one reaction recess210. Each reaction recess 210 can define therein one or more reactionsites and samples 502 can be supported on such reaction sites accordingto one example.

In another aspect, detector 200 can include dielectric stack areas 218,intermediate of the light guides 214. Dielectric stack areas 218 canhave formed therein circuitry, e.g. for read out of signals from lightsensors 202 digitization storage and processing.

According to one example, detector 200 can be provided by a solid-stateintegrated circuit detector, such as complementary metal oxidesemiconductor (CMOS) integrated circuit detector or a charge coupleddevice (CCD) integrated circuit detector.

According to one example, system 100 can be used for performance ofbiological or chemical testing with use of fluorophores. For example, afluid having one or more fluorophores can be caused to flow into and outof flow cell 282 through inlet port using inlet port 289 and outlet port290. Fluorophores can attract to various samples 502 and thus, by theirdetection fluorophores can act as markers for the samples 502 e.g.biological or chemical analytes to which they attract.

To detect the presence of a fluorophore within flow cell 282, lightenergy exciter 10 can be energized so that excitation light 101 in anexcitation wavelength range is emitted by light energy exciter 10. Onreceipt of excitation light 101 fluorophores attached to samples 502radiate emissions signal light 501, which is the signal of interest fordetection by light sensors 202. Emissions signal light 501 owing tofluorescence of a fluorophore attached to a sample 502 will have awavelength range red shifted relative to a wavelength range ofexcitation light 101.

Light energy exciter 10 can include at least one light source and atleast one optical components to illuminate samples 502. Examples oflight sources can include e.g. lasers, arc lamps, LEDs, or laser diodes.The optical components can be, for example, reflectors, dichroics, beamsplitters, collimators, lenses, filters, wedges, prisms, mirrors,detectors, and the like. In examples that use an illumination system,the light energy exciter 10 can be configured to direct excitation light101 to reaction sites. As one example, fluorophores can be excited bylight in the green wavelength range, e.g. can be excited usingexcitation light 101 having a center (peak) wavelength of about 523 nm.

Examples herein recognize that a signal to noise ratio of system 100 canbe expressed as set forth in the equation of (1) hereinbelow.

$\begin{matrix}{{SNR} = \frac{Signal}{\sqrt{\begin{matrix}{{Signal} + {Excitation} + {AF} + {Background} +} \\{{{Dark}\mspace{14mu}{Current}} + {{Read}\mspace{14mu}{{Noise}\hat{}2}}}\end{matrix}}}} & (1)\end{matrix}$where “Signal” is the emissions signal light 501, i.e. the signal ofinterest light attributable to the fluorescence of a fluorophoreattached to a sample, “Excitation” is unwanted excitation light reachingthe light sensors 202, “AF” is the autofluorescence noise radiation ofone or more autofluorescence sources within detector 200, “Background”is unwanted light energy transmitted into detector 200 from a sourceexternal to detector 200, “Dark Current” is current flow is noiseassociated to random electron-hole pair generation in the absence oflight and “Read Noise” is noise associated to analog-to-digitalelectronics.

FIG. 2 is a spectral profile coordination diagram illustrating targetedcoordination between a wavelength range of excitation light, awavelength range of signal light and a detection wavelength range. Inthe spectral profile coordination diagram of FIG. 2 spectral profile1202 is the spectral profile of excitation light 101 as emitted by lightenergy exciter 10. Spectral profile 1204 is the spectrum of absorptionof a fluorophore being detected with use of excitation light 101 havinga spectral profile 1202 and spectral profile 1214 is the spectralprofile of the emissions signal light 501 caused by the fluorescence ofa fluorophore on being excited by excitation light 101. Spectral profile1220 is the transmission profile (detection band) of detector 200 andlight sensors 202 according to one example. Detector 200 can beconfigured to detect light in the wavelength range indicated by spectralprofile 1220. Thus, referring to the spectral profile coordinationdiagram of FIG. 2 , detector 200 is able to detect emissions signallight 501 in the range of wavelengths wherein the spectral profile 1214of the emissions signal light 501 and the detection band spectralprofile 1220 of detector 200 and light sensors 202 intersect.

Detector 200 can include one or more filters that block excitation light101 so that detector 200 having light sensors 202 does not detectexcitation light 101. In one aspect, light guides 214 that guide lightfrom detector surface 206 can comprise filter material so that lightguides 214 block light in the wavelength range of excitation light 101.Light sensors 202 accordingly can receive emissions signal light 501radiating from an excited fluorophore but not excitation light 101.

Examples herein recognize that light guides 214 designed to improve asignal to noise ratio of detector 200 can act as a source of noisewithin detector 200. Referring to the spectral profile diagram of FIG. 3spectral profile 1304 is a spectral profile of a filter material havinga dye that is without (absent) a photon emission quencher commonly usedin optical systems under test by excitation illumination in an expectedwavelength range of excitation light 101 of system 100. In the specificspectral profile diagram of FIG. 3 , spectral profile 1304 illustrates aspectral profile of a filter material under illumination by greenexcitation light, e.g. according to the excitation light spectralprofile 1202 depicted in the spectral profile coordination diagram ofFIG. 2 , having a center (peak) wavelength of about 523 nm.

Referring to the spectral profile diagram of FIG. 3 it is seen that thefilter material having spectral profile characteristics depicted byspectral profile 1304 red shifts with respect to the emission band ofexcitation light 101 depicted by spectral profile 1202 of the spectralprofile coordination diagram of FIG. 2 , meaning that the materialexhibits autofluorescence. Examples herein recognize that with filtermaterial of light guides 214 autofluorescing, signal detected by lightsensors 200 as an emissions signal can actually be noise radiationattributable to excitation light 101 operating to exciteautofluorescence of light guides 214.

Examples to address unwanted autofluorescence of light guides 214 aredescribed with reference to FIGS. 3-7 . Referring to the energy statetransition diagrams of FIGS. 4-6 , light guides 214 according to oneexample can comprise material having a photon emission quencher. Inanother aspect, a filter material can include dye molecules to provideabsorption in a wavelength band of excitation light 101.

The energy state transition diagram of FIG. 4 depicts energy statetransition of a dye without a photon emission quencher. On excitationand after an excitation state relaxation period the dye having theenergy state transition characteristics as depicted in the energy statetransition diagram of FIG. 4 emits photons on return to a ground state.FIG. 5 is an energy state transition diagram depicting energy statetransitions of a dye having a photon emission quencher. Referring to theenergy state transition diagram of FIG. 5 , the dye having a photonemission quencher on excitation returns to a ground state after anexcitation state relaxation period. However, by operation of the photonemission quencher, photons are not released on return to the groundstate. Rather phonons are emitted on return to the ground state. Thereturn to ground state is accompanied by the release of thermal energyrather than photons.

Dyes having the energy state transition characteristics as shown in theenergy state transition diagram of FIG. 4 are radiant dyes and dyeshaving energy state transition characteristics as shown in the energystate transition diagram of FIG. 5 are non-radiant dyes.

A chemical structure diagram of a dye, according to one example, havinga suitable photon emission quencher that quenches photon emissions isshown in (2).

The chemical structural diagram of (2) illustrates structuralcharacteristics of a metal complex dye that functions as a photonemission quencher to quench photon emissions. According to one example,a metal complex dye can be provided by an octahedral transition metalcomplex dye as shown in (2). The specific metal complex dye shown in (2)includes two dye molecules+chromium ion, and some complexes can includeone dye molecule+one chromium (Cr) ion or other metal ion. The structuredepicted in (2) includes six ligand bonds: O, N and a standard crystalfield. According to the structure depicted in (2), there is a photonemission quencher provided by a trivalent Cr transition metal ion.According to one example Cr3+ can provide photon emission quenchingfunctionality. Other transition metals can be used. Transition metalsfor use in a metal complex dye herein can include e.g. Scandium,Titanium, Vanadium, Chromium, Manganese, Iron, Cobalt, Nickel, Copper.For selection of alternative metals, energy levels can be overlappingbetween the metal ion and a dye molecule. According to one example, atransition metal for use in a metal complex dye can be selected to havean absorption spectral profile overlapping a fluorescence emissionsprofile of the selected dye so that the transition metal can providephoton emission quenching functionality through the fluorescenceemission spectral profile of the selected dye.

In the example of the metal complex dye depicted in the structuraldiagram of (2), the metal complex dye has an associated proton depicted.The counter ion associated to the metal complex dye is formed byabsorbing the positive (+) charge specified by the proton of the metalcomplex dye depicted in the structural diagram of (2) and can beselected according to one example for hydrophobicity performance and UVabsorption performance. In one example, an alkyl amine, a primary amine,a secondary amine, or a tertiary amine may associate with the metalcomplex dye forming a counter ion, which can include an alkylammoniumwhen associated with the metal complex dye.

The metal complex dye according to one example may not be particularlysoluble in a solution on its own, and so the counter ion can be chosento increase solubility. The counter ion can be selected forhydrophobicity performance in order to promote transparency andvisibility of the polymer and/or solvent, and for reducing scattering.For instance, the counter ion can allow for the metal complex dye to bemore evenly distributed, enhancing the visibility and transparency, andreducing scattering. The counter ion can be selected for UV absorptionperformance e.g. so that the counter ion does not undesirably contributeto fluorescence. For instance, absorption of the counter ion can affectthe fluorescence characteristics by interfering with the spectrum of themetal dye complex, and can be chosen so as not to have an interferingspectrum. According to one example, a hydrophobic amine can be used as acounter ion. According to another example, it will be understood thatdepending on the metal center and the ligands chosen, a metal complexdye may have no charge, a net positive charge, or may have a netnegative charge as well.

According to one example a counter ion associated to the metal complexdye depicted in the structural diagram of (2) can be provided by analkyl amine. According to one example a counter ion associated to themetal complex dye depicted in the structural diagram of (2) can beprovided by a tertiary amine. In a tertiary amine, a nitrogen has threeorganic substituents. According to one example, a counter ion associatedto the metal complex dye depicted in the structural diagram of (2) canbe provided by a tertiary alkyl amine.

Additionally, in other examples of a metal complex dye, a counter ion ofappropriate charge can be selected to be associated to the metal complexdye. In some embodiments, a negatively or positively charged ion can beselected to counteract the net charge of the metal complex dye molecule,and/or adding to the hydrophobicity in some embodiments to allow for themetal complex dye to be incorporated into a solution. Additionally, whenthere is no charge, no counter ion may be necessary in some embodiments.The counter ion may include any charged particles, and in someembodiments includes primary, secondary, or tertiary amines. In furtherembodiments, a quaternary ammonium ion can be selected.

According to one example, the counter ion associated to the metalcomplex dye as depicted in (2) can include an amine, for instance anNR′R″R′″, where at least one of the R groups is a chain, straight orbranched, with at least four atoms. In some embodiments, there can be atleast 10 atoms in the chain. The chain can include a long chain, and caninclude a polymer. The chain may be a mostly hydrocarbon group, or couldinclude other moieties, such that the dye can possibly be soluble in anysolvent necessary, and the polymer can be soluble in a solvent dependingon the functional groups of the polymer. The other R groups can be thesame or hydrogen, or can comprise a different chain. The chain can beaccording to one example a C4 to C20, including cyclic, chains or rings.In some embodiments, the counter ion can include more than one type ofcounter ion. Examples herein recognize that some mixtures of counterions are convenient for use in solutions where more than one polymermaterial can be used. That is, some alkyl groups can be different, andthe counter ion can include a plurality of counter ions.

FIG. 6 is an energy state transition diagram illustrating properties ofmetal complex dyes. FIG. 6 is an energy state transition diagram for Cr(CN^(tBu)Ar₃NC)₃. Referring to the energy state transition diagram ofFIG. 6 , metal complexes can lead to ultrafast non-radiative(non-autofluorescence) relaxation due to metal centered states beingbelow the metal-2-ligand charge-transfer (MLCT) complex. For Cr(CN^(tBu)Ar₃NC)₃) depicted in the energy state transition diagram inFIG. 6 , the ligand field can be sufficiently weak that metalcentered^(3d-d) excited states can be energetically below the MLCTcomplex leading to ultrafast excited state. Metal complex dyes canexhibit ultrafast excited state depopulation via non-radiativerelaxation. According to the energy state transition diagram of FIG. 6 ametal complex functioning as a photon emission quencher quenches photonsso that a return to ground state is accompanied by phonon emission andrelease of thermal energy rather than photon emission.

To provide filter material, dye molecules in powder form, e.g. havingphoton emission quencher, and according to one example provided by ametal complex dye, can be dissolved with a solvent and added to a liquidpolymer binder to form a liquid matrix having dye molecules and polymermolecules. The liquid can be deposited into a dielectric stack cavity ofdetector 200 and evaporated to form a filter material comprising a soliddye and polymer matrix wherein dye molecules are suspended within amatrix of polymer binder molecules.

A filter material for forming light guide 214 according to one examplecan include metal complex dye molecules suspended in a polymer bindermatrix as set forth herein. A formed filter material including metalcomplex dye molecules suspended in a polymer binder matrix can exhibitspectral profile characteristics under illumination with excitationlight 101 having a center wavelength of about 523 nm as set forth withreference to spectral profile 1404 as shown in the spectral profilediagram of FIG. 3 . According to one example as set forth in referenceto FIG. 3 providing filter material to include a dye having a photonemission quencher (as provided with use e.g. of a metal complex dye) canreduce autofluorescence emissions signals radiating from filter materialat wavelengths of about 570 nm or longer to values that are about 5percent (observing the respective autofluorescence emissions signalvalues of spectral profile 1304 and spectral profile 1404 at awavelength of about 570 nm) or less of their expected values in the casefilter material is provided that includes a dye without a photonemission quencher.

Providing a matrix of dye molecules with a polymer binder moleculefacilitates processability with a range of semiconductor processes e.g.chemical vapor deposition (CVD), spin coating, etching, planarizing, andthe like.

According to one example filter material provided by a metal complex dyematrix can have a weight ratio of between about 70:30 dye to polymer andabout 90:10 dye to polymer. At concentrations above this range, thestructural integrity of the matrix can become compromised and atconcentrations below, filtering performance can become compromised.According to one example filter material provided by a metal complex dyematrix can have a molecule ratio of between about 1 dye molecule:50polymer molecules to about 1 dye molecule:150 polymer molecules.According to one example filter material provided by a polymer binderand metal complex dye matrix can have a molecule ratio of between about1 dye molecule:100 polymer molecules.

While higher concentrations of dye molecules improve blockage ofexcitation light, examples herein recognize that increased scatteringcan be observed at higher concentrations. Light scattering can beaddressed with further processes for filtering powder dye particlesprior to mixing with a polymer binder liquid.

FIG. 7 is an optical density (OD) film thickness diagram illustratingfiltering performance of a filter material herein comprising a matrix ofmetal complex dye suspended in a polymer binder matrix. As seen in theOD film thickness diagram of FIG. 7 , an OD of about 10 can be achievedwithin a spatial budget of 3.5 μm. Referring again to the spectralprofile coordination diagram of FIG. 2 , the spectral profile targetedfor filtering is spectral profile 1202 for excitation light 101 having acenter (peak) wavelength of about 523 nm. Referring to the OD filmthickness diagram of FIG. 7 , by configuring light guide 214 formed of amatrix of metal complex dye suspended in a polymer binder matrix to havea thickness of about 3.5 μm light guide 214 can be configured to exhibitan OD of about 10 for the center (peak) excitation light wavelength ofabout 523 nm. By configuring light guide 214 formed of a matrix of metalcomplex dye suspended in a polymer binder matrix to have a thickness ofabout 2 μm light guide 214 can be configured to exhibit an OD of about 7for the center (peak) excitation wavelength of about 523 nm.

For performance of light sensing, light sensor 202 can have a particularspacing distance in reference to detector surface 206 (FIG. 1 ).According to one example, the particular spacing distance can be aparticular spacing distance in the range, e.g. of from about 4 μm toabout 6 μm. As seen in FIG. 1 , light guides 214 can have spacerestrictions in dependence on the spacing requirements between lightsensors 202 and detector surface 206. In view of the OD thickness datasummarized in the OD film thickness diagram FIG. 7 material forconstruction of light guides 214 can be provided to satisfy targetedoptical density (OD) properties in dependence on spatial properties ofdetector 200, and OD performance suitable for many applications isachievable even where spatial budget is restricted.

As seen by the coordination depicted by the spectral profilecoordination diagram of FIG. 2 , light sensors 202 can sense emissionssignal light 501 attributable to fluorescence of a fluorophore but, inaccordance with ideal operation, cannot detect excitation light 101represented by spectral profile 1202. For configuring of light sensors202 to detect emissions signal light 501 attributable to a fluorophoreattached to a sample 502 without detecting excitation light 101, system100 can include one or more filters. For example, light guides 214 canbe formed of filtering material that blocks light in the energy band ofexcitation light 101 represented by spectral profile 1202. Thus,emissions signal light 501 represented by spectral profile 1214 issubject to detection with use of light sensors 202 without detection ofexcitation light 101. However, as noted, filter material forming lightguide 214 can autofluoresce in response to excitation by excitationlight 101. Examples herein provide light guides 214 to block excitationlight 101 to exhibit reduced autofluorescence so as to preserve desiredspectral profile coordination between excitation fluorescence emissionand detection spectral profiles as depicted in the spectral profilecoordination diagram of FIG. 2 .

Examples herein recognize that left shifting of spectral profile 1220 ofdetector 200 can increase detection of emissions signal light 501 havinga spectral profile indicated by spectral profile 1214 in the spectralprofile of the emissions signal light 501. It should be understood thatas used herein, left shifting refers to hypsochromic shifting, or blueshifting. Filter material herein comprising a matrix of metal complexdye suspended in a polymer binder matrix can be configured for leftshifting of spectral profile 1220 by implementation of various features.In order to left shift spectral profile 1220 certain substituents of theligands surrounding metal complex dye (2) can be altered. For instance,the phenyl groups and other moieties can act as fluorophores, and can sobe altered to left shift the spectrum. For instance, methyl groups canbe replaced with trifluoromethyl or other groups, and hydrogens bereplaced with chlorine or bromine, in some embodiments. The spectrum canbe shifted left or right, depending on the particular metal complex dyeused, by replacing electron donating groups with electrons withdrawinggroups and vice versa. As used herein, right shifting refers tobathochromic shifting, or red shifting, of the spectral wavelength.Thus, in any embodiment, the spectrum can be adjusted with adjustmentsto the functional groups of the metal complex dye.

According to one example, a filter material can include a dye having aphoton emission quencher and the dye can be a non-radiant dye. Accordingto one example, the photon emission quencher can include chromium (Cr).According to one example, the dye can be a metal complex dye having aphoton emission quencher provided by a trivalent Cr transition metalion. According to one example the filter material can be provided bymatrix having a dye and polymer binder, wherein the dye has a photonemission quencher. According to one example the filter material can beprovided by matrix having a dye and polymer binder, wherein the dye is ametal complex dye. According to one example the filter material can beprovided by a dye suspended in a polymer matrix, wherein the dye has aphoton emission quencher. According to one example the filter materialcan be provided by a dye suspended in a polymer matrix, wherein the dyeis a metal complex dye.

Examples herein recognize that performance of system 100 can benegatively impacted by background noise, which herein refers to unwantedlight energy radiating from a source external to detector 200. Examplesherein recognize that a signal to noise ratio of detector 200 can benegatively impacted by fluorescence range background light radiating forsources external to detector 200. Fluorescence range noise emissions insystem 100 can be attributable to sources other than autofluorescingsources within detector 200.

Examples herein recognize for example that while light energy exciter 10can be configured to ideally emit light in a relatively shorterwavelength band, e.g. in a green wavelength band, autofluorescentsources therein, e.g. optical components can autofluoresce and lightthat is emitted by light energy exciter 10 can include unwanted lightrays at longer wavelengths in the fluorescence band of detector 200 andlight sensors 202. Examples herein recognize that fluorescence rangelight can enter system 100 from sources other than light energy exciter10.

In reference to FIG. 8 there are set forth additional features forincreasing a signal to noise ratio of detector 200. In reference to FIG.8 there are described features for cancellation (e.g. partial or entirecancellation) of fluorescence range background noise radiation thatwithout the described features would be received into detector 200.Cancellation features herein can reduce fluorescence range wavelengthssensed by light sensors 202 not attributable to emissions signal light501.

The filter material features set forth in reference to FIGS. 3-7 reducefluorescence range noise by reduction of internal autofluorescencewithin detector 200. Features of detector surface 206 as set forth inconnection with FIG. 8 reduce undesirable fluorescence range backgroundnoise by cancellation (e.g. partial or entire) fluorescence range lightenergy incident on detector surface 206. The features described withreference to FIG. 3-7 can be implemented independently of the featuresof FIG. 8 or according to one example in combination with the featuresof FIG. 8 to address the problem of fluorescence range noise with use ofa combination of detector internal (FIGS. 3-7 ) and detector surface(FIG. 8 ) features.

Now referring to FIG. 8 detector 200 according to one example can beconfigured so that light energy incident on detector surface 206 caninduce electromagnetic fields radiating from detector surface 206 thatcancel (e.g. partially or entirely) incoming light energy which wouldotherwise be transmitted through reaction recess 210. Examples hereinrecognize that behavior of induced fields radiating from detectorsurface 206 induced from light rays incident on detector surface 206 canbecome more controllable and predictable as an index of refraction ratiobetween a detector surface 206 and fluid within flow cell 282 increases.An index of refraction of detector surface 206 can be defined by theindex of refraction of the material of passivation layer 258 adjacentflow cell 282 forming the detector surface 206. Examples hereinrecognize that with a sufficiently high index of refraction ratiobetween detector surface 206 and a fluid of flow cell 282 light rays ofexcitation light 101 can induce electromagnetic fields radiating fromdetector surface 206 that cancel incoming light energy in dependence ona dimension of detector surface 206.

Referring to FIG. 8 , reaction recess 210 can include a dimension “D”provided by the diameter of the reaction recess 210 at a top elevationof reaction recess 210. Examples herein recognize that electromagneticfields induced by incident light energy incident on reaction recess 210can cancel incoming light energy in dependence on the dimension “D”,where an index of refraction ratio between detector surface 206 andfluid within flow cell 282 is sufficiently high. Detector 200 as shownin FIG. 8 can be an integrated circuit detector having structure 260defining detector surface 206 which can include passivation layer 256and passivation layer 258. According to one example where passivationlayer 258 having detector surface 206 is formed of tantalum pentoxide(Ta2O5) having an index of refraction λ206 of about λ206≈2.13 and wherefluid of flow cell 282 is water based and has an index of refractionλ282 of about λ282≈1.33 the index of refraction ratio λ206/λ282 betweena material forming detector surface 206 and a fluid of flow cell 282 isabout λ206/λ282≈1.60. According to one example where passivation layer258 having detector surface 206 is formed of silicon nitride (SiN)having an index of refraction λ206 of about λ206≈2.02 and where fluid offlow cell 282 is water based and has an index of refraction λ282 ofabout λ282≈1.33 the index of refraction ratio λ206/λ282 between amaterial forming detector surface 206 and a fluid of flow cell 282 isabout λ206/λ282≈1.52. A three-dimensional shape of reaction recess 210can be cylindrical or frustro-conical in some examples such that across-section taken along a horizontal plane that extends into the pageof FIG. 8 is substantially circular. A longitudinal axis 268 can extendthrough a geometric center of the cross-section.

Examples herein recognize that for a detector surface 206 as set forthin FIG. 8 having a reaction recess 210 (nanowell) with the dimension Dand with an index of refraction ratio λ206/λ282 suitably high there is acritical wavelength λc wherein wavelengths shorter than the criticalwavelength λc are transmitted into an interior of reaction recess 210and detector 200 and wherein wavelengths longer than the criticalwavelength λc are cancelled (e.g. partially cancelled or entirelycancelled) by detector surface 206 having reaction recess 210. Examplesherein further recognize that the described critical wavelength λc is independence of the dimension D so that the dimension D can be controlledto tune the critical dimension λc to a desired value. More specificallythe critical wavelength λc can be increased by increasing the dimensionD and the critical wavelength λc can be decreased by decreasing thedimension D. Without being bound to a particular theory in regard to therecognized effect, light rays incident on detector surface 206 mayinduce electromagnetic fields radiating from detector surface 206 thatcancel (e.g. partially or entirely) incoming light energy which wouldotherwise be transmitted through reaction recess 210.

Light energy cancellation features can be advantageously incorporatedinto the design of detector surface 206. According to one exampledescribed with reference to FIG. 8 the dimension D can be selected toestablish the critical wavelength λc so that wavelengths at about thecenter (peak) wavelength of excitation light 101 and shorter aretransmitted through reaction recess 210 and into detector 200 andfurther so that wavelengths of about the shortest detection bandwavelength λb and longer are cancelled by detector surface 206.Transmission of wavelengths at about the center (peak) wavelength ofexcitation light 101 and shorter can assure that fluorophores areproperly excited according to the design of system 100 and cancellationof wavelengths of about the shortest detection band wavelength λb andlonger can increase a signal to noise ratio of detector 200.

While λc can be tuned in dependence on D, the precise relationshipbetween D and cancellation effects in dependence thereon can varydepending on materials, configuration (including light energy exciter 10configuration), and process control parameters of a particularlyfabricated system 100. Notwithstanding, information of the relationshipbetween the dimension D and a cancellation effect in dependence thereonfor a particular design of detector 200 can be determined byexperimentation. On determination of information by experimentation thatspecifies a relationship between D and a cancellation effect for aparticular design of detector 200, the information can be used toestablish a value for D; that is, D=d1 where D=d1 is selected toestablish the critical wavelength λc so that wavelengths at about acenter (peak) wavelength λc of excitation light 101 and shorter aretransmitted into reaction recess 210 and detector 200 and further sothat wavelengths of about the shortest detection band wavelength λb andlonger (i.e. in the fluorescence range) are cancelled by detectorsurface 206.

According to one process, one or more test sample detectors according todetector 200 can be fabricated and subject to test. The test can includetesting for transmission of excitation light 101 by reaction recess 210.One or more test samples can be provided and subject to testing todetermine the smallest dimension of D, D=dc at which reaction recess 210transmits excitation light 101 in accordance with one or moretransmission criterion. The one or more transmission criterion can bee.g. that a threshold amount (e.g. 90 percent, 100 percent) of maximumenergy excitation light 100 is transmitted through reaction recess 210.One or more test samples can be provided and subject to testing todetermine the largest dimension of D, D=de at which reaction recess 210cancels fluorescence range light (e.g. a discernible amount offluorescence range light) in a detection band of light sensors 102. Forsuch testing signals read out by light sensors 202 can be examined withlight guides 214 fabricated according to their productionspecifications. With one or more of dimensions D=dc or D=de determined,detector 200 according to a production design can be provided. In theproduction design according to one example, D=d1 can be provided to bein the range of from about D=dc to about D=de. In the production designaccording to one example, D=d1 can be provided to be at about themidpoint distance of between D=dc and D=De. In the production designaccording to one example, D=d1 can be provided to be about D=dc. In theproduction design according to one example, D=d1 can be provided to beabout D=de. In the described examples, the dimension D can be providedto establish a critical wavelength λc so that λc is within a range ofwavelengths of between about λa and about λb, wherein wavelengthsshorter than λc are transmitted by reaction recess 210 and whereinwavelengths longer than λc are cancelled by reaction recess 210, whereinλa is the center wavelength of excitation light 101 and wherein λb isthe shortest detection band wavelength of the sensor array 201.

Referring to the spectral profile coordination diagram of FIG. 2 ,excitation light 101 can have a center (peak) wavelength of about 523 nm(λa), and detector 200 with light sensors 202 can have a detection bandcommencing at about 580 nm (shortest detection band wavelength λb).Thus, reaction recess 210 according to one example, configured to have asuitable index of refraction, can be dimensioned to permit entry ofincident light energy at wavelengths of about 523 nm and shorter and canbe dimensioned to cancel incident light energy at wavelengths of about580 nm and longer. In the case where detector 200 is of a configurationwherein D=d1≈λc so that the distance d1 is in common with the criticalwavelength λc, D can be dimensioned according to D=550 nm to transmitexcitation light 101 into reaction recess 210 and to cancel unwantedfluorescence range wavelengths according to the spectral profilecoordination diagram of FIG. 2 . With the described configuration, thedetector surface 206 can be dimensioned to permit entry of incidentlight energy at wavelengths of about 523 nm and shorter and can bedimensioned to cancel incident light energy at wavelengths of about 580nm and longer.

There is set forth herein a method including subjecting a test sampledetector according to detector 200 (having a structure 260 definingdetector surface 206) to determine information that specifies arelationship between a dimension e.g. D of detector surface 206 and anelectromagnetic field cancellation effect (e.g. including informationsuch dc, de and/or other information relating D to λc) and wherein thefabricating the structure 260 defining a detector surface 206 includesdimensioning, using the determined information, a reaction recess 210 ofthe detector surface 206 to transmit excitation light 101 in anexcitation wavelength band of excitation light 101 (including at thecenter (peak) wavelength λa) and to cancel light energy incident on thedetector surface 206 in a detection band of the light sensor array 201.

A three-dimensional shape of reaction recess 210 can be cylindrical orfrustro-conical in some examples such that a cross-section taken along ahorizontal plane that extends into the page of FIG. 8 is circular. Alongitudinal axis 268 can extend through a geometric center of thecross-section. However, other geometries can be used in alternativeexamples. For example, the cross-section can be square-shaped oroctagonal. According to one example, shield structure 250 can have athickness of from about 100 nm to about 600 nm, passivation layer 256can have a thickness of from about 100 nm to about 600 nm, passivationlayer 256 can have a thickness of from about 50 nm to about 500 nm,aperture 252 can have a diameter of from about 700 nm to about 1.5 μm,and reaction recess 210 if present can have a height H of from about 50nm to about 500 nm.

FIGS. 9 and 10 illustrate further details of an example of detector 200having one or more fluorescence range noise reducing features as setforth herein.

Referring to FIGS. 9-10 there is set forth herein a detector surface 206for supporting biological or chemical substances; a sensor array 201comprising light sensors 202, and circuitry 246 to transmit data signalsbased on photons detected by the light sensors 202; a guide array 213comprising light guides 214; wherein light guides 214 of the guide array213 receive excitation light 101 and emissions signal light 501 from thedetector surface 206, wherein the light guides 214 extend towardrespective light sensors 202 of the sensor array 201 and comprise filtermaterial that blocks the excitation light 101 and permits emissionssignal light 501 radiating from fluorescing fluorophores to propagatetoward the respective light sensors 202, wherein the detector surfaceincludes a reaction recess 210, the reaction recess comprising an indexof refraction and a dimension to cancel background light energy incidenton the detector surface in a detection band of the sensor array 201.

Detector 200 can include a sensor array 201 of light sensors 202, aguide array 213 of light guides 214, and a reaction array 209 ofreaction recesses 210. In certain examples, the components are arrangedsuch that each light sensor 202 aligns with a single light guide 214 anda single reaction recess 210. However, in other examples, a single lightsensor 202 can receive photons through more than one light guide 214. Insome examples there can be provided more than one light guide and/orreaction recess for each light sensor of a light sensor array. In someexamples there can be provided more than one light guide and/or lightsensors aligned to a reaction recess of a reaction recess array. Theterm “array” does not necessarily include each and every item of acertain type that the detector can have. For example, the sensor arrayof light source may not include each and every light sensor of detector200. As another example, the guide array 213 may not include each andevery light guide of detector 200. As another example, the reactionarray 209 may not include each and every reaction recess 210 of detector200. As such, unless explicitly recited otherwise, the term “array” mayor may not include all such items of detector 200.

In the illustrated example, flow cell 282 is defined by sidewall 284 anda flow cover 288 that is supported by the sidewall 284 and othersidewalls (not shown). The sidewalls are coupled to the detector surface206 and extend between the flow cover 288 and the detector surface 206.In some examples, the sidewalls are formed from a curable adhesive layerthat bonds the flow cover 288 to detector 200.

The flow cell 282 can include a height H1. By way of example only, theheight H1 can be between about 50-400 μm or, more particularly, about80-200 μm. The flow cover 288 can include a material that is lighttransmissive to excitation light 101 propagating from an exterior of thedetector assembly 20 into the flow cell 282.

Also shown, the flow cover 288 can define inlet and outlet ports 289,290 that are configured to fluidically engage other ports (not shown).For example, the other ports can be from a cartridge (not shown) or aworkstation (not shown).

Detector 200 has a detector surface 206 that can be functionalized (e.g.chemically or physically modified in a suitable manner for conductingdesignated reactions). For example, the detector surface 206 can befunctionalized and can include a plurality of reaction sites having oneor more biomolecules immobilized thereto. The detector surface 206 canhave a reaction array 209 of reaction recesses 210. Each of the reactionrecesses 210 can include one or more of the reaction sites. The reactionrecesses 210 can be defined by, for example, an indent or change indepth along the detector surface 206. In other examples, the detectorsurface 206 can be planar.

FIG. 10 is an enlarged cross-section of detector 200 showing variousfeatures in greater detail. More specifically, FIG. 10 shows a singlelight sensor 202, a single light guide 214 for directing emissionssignal light 501 toward the light sensor 202, and associated circuitry246 for transmitting signals based on emissions signal light 501 (e.g.photons) detected by the light sensor 202. It is understood that theother light sensors 202 of the sensor array 201 (FIG. 9 ) and associatedcomponents can be configured in an identical or similar manner. It isalso understood, however, the detector 200 is not required to bemanufactured identically or uniformly throughout. Instead, one or morelight sensors 202 and/or associated components can be manufactureddifferently or have different relationships with respect to one another.

The circuitry 246 can include interconnected conductive elements (e.g.conductors, traces, vias, interconnects, etc.) that are capable ofconducting electrical current, such as the transmission of data signalsthat are based on detected photons. Detector 200 comprises an integratedcircuit having a planar array of the light sensors 202. The circuitry246 formed within detector 200 can be configured for at least one ofread out signals from light sensors 202 after an exposure period(integration period) in which charge accumulates on light sensor 202,signal amplification, digitization, storage, and processing. Thecircuitry 246 can collect and analyze the detected emissions signallight 501 and generate data signals for communicating detection data toa bioassay system. The circuitry 246 can also perform additional analogand/or digital signal processing in detector 200. Light sensors 202 canbe electrically coupled to circuitry 246 through gates 241-243.

Detector 200 according to one example can be provided by a solid-stateintegrated circuit detector such as a CMOS integrated circuit detectoror a CCD integrated circuit detector. Detector 200 according to oneexample can be an integrated circuit chip manufactured using integratedcircuit manufacturing processes such as complementary metal oxidesemiconductor (CMOS) fabrication processes.

The resolution of the sensor array 201 defined by light sensors 202 canbe greater than about 0.5 megapixels (Mpixels). In more specificexamples, the resolution can be greater than about 5 Mpixels and, moreparticularly, greater than about 14 Mpixels.

Detector 200 can include a plurality of stacked layers 231-237 includinga sensor layer 231, which can be a silicon layer. The stacked layers caninclude a plurality of dielectric layers 232-237. In the illustratedexample, each of the dielectric layers 232-237 includes metallicelements (e.g. W (tungsten), Cu (copper), or Al (aluminum)) anddielectric material, e.g. SiO2. Various metallic elements and dielectricmaterial can be used, such as those suitable for integrated circuitmanufacturing. However, in other examples, one or more of the dielectriclayers 232-237 can include only dielectric material, such as one or morelayers of SiO2.

With respect to the specific example of FIG. 10 , the dielectric layers232-237 can include metallization layers that are labeled as layersM1-M5 in FIG. 10 . As shown, the metallization layers, M1-M5, can beconfigured to form at least a portion of the circuitry 246.

In some examples, detector 200 includes a shield structure 250 havingone or more layers that extend throughout an area above metallizationlayer M5. In the illustrated example, the shield structure 250 caninclude a material that is configured to block, reflect, and/orsignificantly attenuate the light signals that are propagating from theflow cell 282. The light signals can be the excitation light 101 and/oremissions signal light 501. By way of example only, the shield structure250 can comprise tungsten (W). By way of specific example only, theexcitation light 101 may have a center (peak) wavelength of about 523 nmand emissions signal light 501 can include wavelengths of about 570 nmand longer (FIG. 2 ).

As shown in FIG. 10 , shield structure 250 can include an aperture 252therethrough. The shield structure 250 can include an array of suchapertures 252. Aperture 252 is dimensioned to allow signal emissionlight to propagate to light guide 214. Detector 200 can also include apassivation layer 256 that extends along the shield structure 250 andacross the apertures 252. Detector 200 can also include a passivationlayer 258 comprising detector surface 206 that extends along passivationlayer 256 and across the apertures 252. Shield structure 250 can extendover the apertures 252 thereby directly or indirectly covering theapertures 252. Passivation layer 256 and passivation layer 258 can beconfigured to protect lower elevation layers and the shield structure250 from the fluidic environment of the flow cell 282. According to oneexample, passivation layer 256 is formed of SiN or similar. According toone example, passivation layer 258 is formed of tantalum pentoxide(Ta2O5) or similar. Structure 260 having passivation layer 256 andpassivation layer 258 can define detector surface 206 having reactionrecesses 210. Structure 260 defining detector surface 206 can have anynumber of layers such as one to N layer.

Structure 260 can define a solid surface (i.e., the detector surface206) that permits biomolecules or other analytes-of-interest to beimmobilized thereon. For example, each of the reaction sites of areaction recess 210 can include a cluster of biomolecules that areimmobilized to the detector surface 206 of the passivation layer 258.Thus, the passivation layer 258 can be formed from a material thatpermits the reaction sites of reaction recesses 210 to be immobilizedthereto. The passivation layer 258 can also comprise a material that isat least transparent to a desired fluorescent light. Passivation layer258 can be physically or chemically modified to facilitate immobilizingthe biomolecules and/or to facilitate detection of the emissions signallight 501.

In the illustrated example, a portion of the passivation layer 256extends along the shield structure 250 and a portion of the passivationlayer 256 extends directly along filter material defining light guide214. The reaction recess 210 can be aligned with and formed directlyover light guide 214. According to one example each of reaction recess210 and light guide 214 can have geometric centers centered onlongitudinal axis 268.

As set forth herein in connection with FIG. 8 detector surface 206 canbe dimensioned so that light energy incident on detector surface 206 ina fluorescence range can be cancelled by the operation of inducedelectromagnetic fields. According to one example, shield structure 250can have a thickness of from about 100 nm to about 600 nm, passivationlayer 256 can have a thickness of from about 100 nm to about 600 nm,passivation layer 256 can have a thickness of from about 50 nm to about500 nm, aperture 252 can have a diameter of from about 700 nm to about1.5 μm, and reaction recess 210 if present can have a height of fromabout 50 nm to about 500 nm.

In some cases, prior to the passivation layer 256 being deposited alongthe shield structure 250, and prior to a depositing of shield structure250 a cavity defined by sidewalls 254 can be formed the dielectric stackdefined by dielectric layers 232-237. For example, the dielectric stackdefined by dielectric layers 232-237 can be etched to form an array ofthe cavities defined by sidewalls 254, wherein one cavity is formed foreach light sensor 202 of light sensor array 201. In particular examples,a cavity defined by sidewalls 254 is a vertically elongated space thatextends from proximate the aperture 252 toward the light sensor 202.

The cavity can extend vertically along longitudinal axis 268. Athree-dimensional shape of cavity defined by sidewalls 254 can becylindrical or frustro-conical in some examples such that across-section taken along a horizontal plane that extends into the pageof FIG. 10 is circular. The longitudinal axis 268 can extend through ageometric center of the cross-section. However, other geometries can beused in alternative examples. For example, the cross-section can besquare-shaped or octagonal. According to one example the longitudinalaxis 268 which is the longitudinal axis of light guide 214 can extendthrough a geometric center of light sensor 202 and reaction recess 210.

The filter material defining light guide 214 can be deposited within thecavity defined by sidewalls 254 after the cavity defined by sidewalls254 is formed. For fabrication of light guide 214 according to oneexample, dye molecules in powder form, e.g. having photon emissionquencher, can be dissolved with a solvent and added to a liquid polymerbinder to form a homogeneous liquid matrix having dye molecules andpolymer molecules. According to one example the dye molecules in powderform can be metal complex dye particles.

The homogeneous liquid matrix can be deposited into a dielectric stackcavity of detector 200 and evaporated to form a filter materialcomprising a solid dye and polymer matrix wherein dye molecules aresuspended within a matrix of polymer binder molecules. The homogeneouspolymer binder and dye matrix filter material can be deposited into thecavity defined by sidewalls 254, using e.g. chemical vapor deposition(CVD) physical vapor deposition (PVD). The depositing can be performedto overfill the cavity defined by sidewalls 254 with filter material andthen subject to patterning such as by planarization or etching to reducethe elevation of the filter material defining light guide 214. A filtermaterial for forming light guide 214 according to one example caninclude metal complex dye molecules suspended in a polymer bindermolecule matrix.

The filter material can form (e.g. after curing) a light guide 214. Thelight guide 214 can be configured to block the excitation light 101 andpermit emissions signal light 501 (FIG. 1 ) to propagate therethroughtoward the corresponding light sensor 202. The light guide 214 can beformed of filter material described in reference to FIGS. 2-7 herein.The filter material can include a homogeneous matrix of dye and polymerbinder, wherein the dye can include a photon emission quencher andaccording to one example is provided by a metal complex dye. The dye andpolymer matrix according to one example can include a weightconcentration in the range of from about 70:30 dye to polymer to about90:10 dye to polymer. The filter material mixture can have a moleculeratio of about 1 dye molecule to about 100 polymer molecules.

The light guide 214 can be configured relative to surrounding materialof the dielectric stack defined by dielectric layers 231-237 to form alight-guiding structure. For example, the light guide 214 can have arefractive index of at least about 2.0 so that light energy propagatingthrough light guide is reflected at an interface between light guide 214and the surrounding dielectric stack defined by dielectric layers231-237. In certain examples, the light guide 214 is configured suchthat the optical density (OD) or absorbance of the excitation light 101is at least about 4 OD. More specifically, the filter material can beselected and the light guide 214 can be dimensioned to achieve at least4 OD. In more particular examples, the light guide 214 can be configuredto achieve at least about 5 OD or at least about 6 OD. In moreparticular examples, the light guide 214 can be configured to achieve atleast about 5 OD or at least about 6 OD. Other features of the detector200 can be configured to reduce electrical and optical crosstalk.

It should be appreciated that all combinations of the foregoing conceptsand additional concepts discussed in greater detail below (provided suchconcepts are not mutually inconsistent) are contemplated as being partof the subject matter disclosed herein. In particular, all combinationsof claims subject matter appearing at the end of this disclosure arecontemplated as being part of the subject matter disclosed herein. Itshould also be appreciated that terminology explicitly employed hereinthat also may appear in any disclosure incorporated by reference shouldbe accorded a meaning most consistent with the particular conceptsdisclosed herein.

This written description uses examples to disclose the subject matter,and also to enable any person skilled in the art to practice the subjectmatter, including making and using any devices or systems and performingany incorporated methods. The patentable scope of the subject matter isdefined by the claims, and can include other examples that occur tothose skilled in the art. Such other examples are intended to be withinthe scope of the claims if they have structural elements that do notdiffer from the literal language of the claims, or if they includeequivalent structural elements with insubstantial differences from theliteral languages of the claims.

It is to be understood that the above description is intended to beillustrative, and not restrictive. For example, the above-describedexamples (and/or aspects thereof) can be used in combination with eachother. In addition, many modifications can be made to adapt a particularsituation or material to the teachings of the various examples withoutdeparting from their scope. While the dimensions and types of materialsdescribed herein are intended to define the parameters of the variousexamples, they are by no means limiting and are merely exemplary. Manyother examples will be apparent to those of skill in the art uponreviewing the above description. The scope of the various examplesshould, therefore, be determined with reference to the appended claims,along with the full scope of equivalents to which such claims areentitled. In the appended claims, the terms “including” and “in which”are used as the plain-English equivalents of the respective terms“comprising” and “wherein.” Moreover, in the following claims, the terms“first,” “second,” and “third,” etc. are used merely as labels, and arenot intended to impose numerical requirements on their objects. Forms ofterm “based on” herein encompass relationships where an element ispartially based on as well as relationships where an element is entirelybased on. Forms of the term “defined” encompass relationships where anelement is partially defined as well as relationships where an elementis entirely defined. Further, the limitations of the following claimsare not written in means-plus-function format and are not intended to beinterpreted based on 35 U.S.C. § 112, sixth paragraph, unless and untilsuch claim limitations expressly use the phrase “means for” followed bya statement of function void of further structure. It is to beunderstood that not necessarily all such objects or advantages describedabove can be achieved in accordance with any particular example. Thus,for example, those skilled in the art will recognize that the systemsand techniques described herein can be embodied or carried out in amanner that achieves or optimizes one advantage or group of advantagesas taught herein without necessarily achieving other objects oradvantages as can be taught or suggested herein.

While the subject matter has been described in detail in connection withonly a limited number of examples, it should be readily understood thatthe subject matter is not limited to such disclosed examples. Rather,the subject matter can be modified to incorporate any number ofvariations, alterations, substitutions or equivalent arrangements notheretofore described, but which are commensurate with the spirit andscope of the subject matter. Additionally, while various examples of thesubject matter have been described, it is to be understood that aspectsof the disclosure can include only some of the described examples. Also,while some examples are described as having a certain number of elementsit will be understood that the subject matter can be practiced with lessthan or greater than the certain number of elements. Accordingly, thesubject matter is not to be seen as limited by the foregoingdescription, but is only limited by the scope of the appended claims.

The invention claimed is:
 1. A device comprising: a detector surfaceconfigured for supporting biological or chemical samples; a sensor arraycomprising light sensors and light guides; wherein the light guidesreceive excitation light and emissions signal light from the detectorsurface, wherein the light guides extend toward respective light sensorsof the sensor array and comprise filter material, and wherein the filtermaterial comprises a dye having a transition metal, and wherein thetransition metal has an absorption spectral profile overlapping afluorescence emissions spectral profile of the dye.
 2. The device ofclaim 1, wherein the dye is suspended in a polymer binder matrix.
 3. Thedevice of claim 1, wherein the filter material comprises a homogeneousmatrix of the dye and a polymer binder and wherein the homogeneousmatrix comprises a weight concentration ratio of dye to polymer binderin the range of from about 70:30 to about 90:10.
 4. The device of claim1, wherein the detector surface includes a reaction recess forsupporting a sample, wherein the reaction recess comprises an index ofrefraction and dimension to cancel background radiation in a detectionband of the sensor array.
 5. The device of claim 1, wherein the filtermaterial comprises a counter ion associated to the transition metal. 6.The device of claim 5, wherein the counter ion comprises an alkyl aminehaving at least one hydrocarbon group of at least four carbon atoms. 7.A method comprising: depositing filter material within guide cavities ofa guide cavity array that are aligned with and disposed above respectivelight sensors of a light sensor array, wherein the filter materialcomprises a dye having a transition metal, and wherein the transitionmetal has an absorption spectral profile overlapping a fluorescenceemissions spectral profile of the dye; and fabricating a structuredefining a detector surface for supporting biological or chemicalsamples above cavities of the guide cavity array and light sensors ofthe light sensor array.
 8. The method of claim 7, wherein the depositingfilter material comprises using chemical vapor deposition, and whereinsubsequent to the depositing, the deposited filter material is subjectto processing using one or more of etching and planarizing.
 9. Themethod of claim 7, wherein the filter material comprises a homogeneousmatrix of the dye and polymer binder.
 10. The method of claim 7, whereinthe filter material comprises a matrix of the dye and polymer binder andwherein a weight concentration of dye to polymer binder is in the rangeof from about 70:30 to about 90:10.
 11. The method of claim 7, whereinthe fabricating a structure defining a detector surface comprisesforming a reaction recess defined in the detector surface, wherein theforming includes configuring the reaction recess so that based on anindex of refraction of the detector surface and a dimensionalcharacteristic of the reaction recess, an induced electromagnetic fieldradiating from the detector surface cancels background light energyincident on the detector surface in a detection wavelength band of thelight sensor array.
 12. The method of claim 7, wherein the methodincludes subjecting one or more test sample detectors to testing todetermine information relating a dimension of a detector surface to anelectromagnetic field cancellation effect and wherein the fabricatingthe structure defining a detector surface includes dimensioning, usingthe determined information, a reaction recess of the detector surface tocancel light energy incident on the detector surface in a detection bandof the light sensor array.
 13. The method of claim 7, wherein the filtermaterial comprises a counter ion associated to the dye.
 14. The methodof claim 13, wherein the counter ion comprises an alkyl amine having atleast one hydrocarbon group of at least four carbon atoms.